tbuckley/cabot-search huggingface dataset:
KEVLAR: A phase 2b, multi-institutional, randomized, blinded, controlled trial to assess the safety and efficacy of two schedules of RRx-001 vs. standard of care in attenuating severe oral mucositis (SOM) in patients receiving concomitant chemoradiation (CRT) for the treatment of locally advanced squamous cell carcinomas (SCC) of the oral cavity (OC) or oropharynx (OPC).
Authors: Tony R. Reid, Bryan Oronsky, Scott Caroen, Nacer Abrouk, Meaghan Stirn, Stephen T. Sonis
Journal: Journal of Clinical Oncology (2023)

TPS6113 Background: The results of an open-labeled Phase 2a trial suggested that infusion of RRx-001 (bromonitrozidine), a nitrogen-containing NLRP3 inhibitor and Nrf2 activator, attenuated the course and severity of SOM associated CRT (cisplatin/IMRT) in cancers of the mouth or OPC without impeding tumor response. The primary efficacy objectives of KEVLAR are to replicate the findings of the earlier trial and to determine if a higher dose of RRx-001 (8 mg x 4 doses prior to CRT) will favorably impact overall SOM incidence. Methods: KEVLAR is a planned Phase 2b study to be conducted at about thirty sites in North America. Approximately 216 patients with pathologically confirmed SCCs of the OC or OPC will be randomized equally into one of 3 cohorts: Arm 1 will receive RRx-001, 8 mg/dose infusions twice weekly during the 2 weeks prior to CRT start; Arm 2 will receive RRx-001, 4 mg/dose in the same schedule; Arm 3 will receive best supportive care only. All patients will receive intensity modulated radiation therapy (IMRT) in 2.0-2.2 Gy fractions/weekday to a cumulative radiation dose of up to 72 Gy. CRT must include cisplatin administered either weekly (40 mg/m 2 ) or tri-weekly (100 mg/m 2 ). Radiation fields must include at least two oral sites at SOM risk planned to receive at least 55 Gy. Mucositis indicators will be assessed twice weekly by trained evaluators. OM will be scored centrally using WHO criteria from the first day of CRT until resolution of ulcerative OM (WHO grade ≤1). Adverse events will be evaluated using NCICTCv5 criteria. Patients will be followed for 24 months post the last day of radiation and tumor response will be recorded quarterly using RECIST criteria.
Patients’ epidemiology in stage III, unresectable non-small-cell lung carcinoma: A real-world analysis in Brazil.
Authors: Flavia Amaral Duarte, André Marques dos Santos, Pamela Santana, Caique Dias, Danilo Lopes, Priscila Denapoli
Journal: Journal of Clinical Oncology (2023)

e20589 Background: Although breakthrough therapy options for NSCLC have emerged in the last few years, lung cancer is still the principal cause of cancer-related deaths in both men and women worldwide. In Brazil, lung cancer is the major cause of cancer mortality – the second most common cause of cancer-related death in females and the first cause among males. The main factors contributing to the high burden of the disease remain the late-stage diagnosis and unequal healthcare access, which are most prevalent in low- and middle-income countries. This study aimed to describe lung cancer epidemiology – patients in stage III, unresectable NSCLC that could benefit from consolidation therapy after chemoradiation (CRT) treatment - in the Brazilian public health system for evaluating the future impact of new therapies. Methods: We gathered information on lung cancer procedures performed between January 2018 and October 2022 using the Brazilian public health system database (DATASUS). Since this is a claim medical database without clinical data, assumptions were specified based on procedures performed to determine the potential number of patients in Brazil who would benefit from these new treatment strategies in stage III NSCLC. The assumptions were the following: 1. Having received systemic therapy for a malignant tumor of the bronchi and lung (ICD-10 - C34); 2. Having received a pre-defined list of chemotherapy regimens (to define which patients were NSCLC); 3. Having started systemic therapy with a Stage III tumor; 4. Having not undergone surgery between three months before and two months following the start of systemic treatment 5. Treated with chemotherapy and radiotherapy (concomitantly or sequentially - until two months later); 6. Patients who died or progressed during treatment were classified as incomplete treatment. Results: Between 2018 and 2022, we identified an average of 9,340 patients each year who started therapies for lung cancer; 75% (7,023) of them performed specific procedures for NSCLC and were classified as such. 21% (1,472) of patients started treatment for stage III NSCLC, and 98% (1,438) of these cases were unresectable. Of these, 26% (377) received chemotherapy and radiation, 92% of whom finished the course of treatment. In Brazil, 346 patients per year with stage III unresectable NSCLC could be treated with consolidation therapy after CRT in the public health system. Conclusions: The number of NSCLC patients who can benefit from consolidation therapy after CRT (346) represents 3.7% of all lung cancer patients starting systemic treatment annually. It allows a better management of the possible economic impact of the addition of this new therapy in the Brazilian health public system. Increased screening for early diagnosis and improving access to CRT would expand the patient population eligible for this therapeutic approach.
Defining and implementing meaningful advance care planning.
Authors: Emma Hannan, Elizabeth Collins, Valerie Pracilio Csik, Greg D. Garber, Ramona Sitko, Rebecca Cammy, Brooke Worster
Journal: Journal of Clinical Oncology (2023)

e18708 Background: Advance Care Plans (ACP) capture a patient’s preferences for care before the patient becomes unable to make their own decisions. Our center (SKCC) participates in external quality programs, including the ASCO Oncology Medical Home model and CMS’ Oncology Care Model, that require ACP among cancer patients. Evidence from other centers suggest ACP, as defined by these external programs, do not impact patient outcomes. In an effort to increase the rate of “meaningful” ACP our interdisciplinary team completed an iterative quality improvement (QI) project to define an internal, more rigorous standard of ACP. Methods: Clinicians at SKCC developed a standardized Personalized Care Discussion (PCD) appointment conversation template to guide meaningful, goals-based care discussions with cancer patients. Our project assessed the rate at which different patients completed a scheduled PCD appointment between 6/2/2021 and 7/1/2022. The objectives of our QI project were to: identify a sub-population of cancer patients with the highest expected value from PCD; and define an evidence-based metric to hold care teams accountable for completing PCD. Our interdisciplinary QI project team monitored and evaluated 5 cycles of plan-do-study-act (PDSA) over the course of 1 year to meet the project objectives. Each PDSA included either an adjustment to the patient population or an adjustment to the workflow. The key performance indicator in each PDSA was the % of patients with a scheduled PCD appointment who completed the appointment. Results: Of the all the PDSA cycles, the ones with the highest completion rate of a scheduled PCD appointment were cycles in which: the patient’s oncologist introduced the patient to PCD (as opposed to automated scheduling); and the patient was introduced to PCD early on in their care at SKCC. Conclusions: The results of this project led us to develop an internal quality metric that requires oncology providers (OP) facilitate PCD with all new cancer patients within 9 months of the new patient visit. This metric exceeds expectations of external programs by requiring OPs complete goals-based ACP with patients and introducing ACP as a universal standard of cancer care for all new patients. Operational support for OPs is critical for success in this initiative. Patient education that manages sensitivities and stigma about ACP enhances successful OP-patient collaboration. SKCC continues to monitor the impact of this metric on patient outcomes. [Table: see text]
Clinical validation of next-generation sequencing-based clonality assays for minimal residual disease tracking in multiple myeloma.
Authors: Chuanming Lin, Qijie Jian, Zoufang Huang, Shuiling Xie, Liuyan Xin, Haiyan Wu, Fei Pang, Changfeng Liao, Yijian Chen
Journal: Journal of Clinical Oncology (2023)

e20037 Background: The prognosis of multiple myeloma (MM) patients is dependent on minimal residual disease (MRD) status after treatment. Multicolor flow cytometry (MFC) as a clinical MRD evaluation method has certain limitations regarding sample requirement, sensitivity and specificity. Next-generation sequencing (NGS)-based B cell receptor (BCR) clonality assessment has an edge in lymphoid clone MRD detection, with easier sample preparation and higher sensitivity. NGS-based BCR clonality assays were performed to evaluate curative effect and track MRD of MM patients, and its performance in testing samples with limited DNA contents was explored. Methods: In this retrospective study, newly diagnosed or relapsed MM patients with paired sample collected before and after initial treatment were included, and OriMIRACLE L NGS assay were used for BCR clonality detection in genomic DNA (gDNA) extracted from clinical residual marrow smear samples. The quantitative accuracy of NGS was compared to MFC. The concordance of MRD between MFC, NGS and clinical response assessment were analyzed. Results: From December 2016 to April 2022, 29 patients were included with a median age of 65 years old. The gDNA input of the sample collected before treatment was 100.0 ng, and the median DNA content of the sample collected after treatment was 1673.4 ±594.8 ng. The quantitative results of NGS and MFC were consistent in samples with a frequency of cancer cells of above 1x10 -4 among all nucleated cells. BCR clonality detection in 23 newly diagnosed and 6 relapsed cases showed a 100% sensitivity at diagnosis. For post-treatment monitoring, patients with positive MRD by both MFC and NGS (n = 18), the MRD results were consistent with clinical response assessment. One of the patients achieved complete response (CR), while the remaining patients were unable to achieved CR. The CR patient was relapsed after 134 days. The clinical responses of 11 cases with negative MRD by MFC and positive MRD by NGS were reviewed. There were 7 cases with CR, 3 cases with very good partial response or partial response, and one case with stable disease. Among those CR patients, except for one patient who was lost to follow-up, 4 patients who underwent continuous treatment were still CR and 2 patients who had treatment discontinued recurred at 67 and 134 days. Conclusions: OriMIRACLE L NGS assay showed the higher sensitivity and specificity of MRD evaluation than MFC. For patients with negative MRD by MFS and positive MRD by NGS, recurrence might occur in case of treatment discontinuation. It is recommended to consider carefully that whether maintenance treatment is required in such cases.
Sensitive detection of CSF-derived cell-free DNA at the CNV level by shallow whole-genome sequencing for diagnosis and characterization of CNS metastases.
Authors: Li Yubin, Zongkun Shi, Juan An, Weiran Xu, Yichun Hua, Xixi Zheng, Xiaosheng Ding, Hui Shi, Yanli Nie, Lili Zhou, Dandan Cao, Xiaoyan Li
Journal: Journal of Clinical Oncology (2023)

e21185 Background: The cfDNA targeted capture sequencing technology has been gradually applied to research central nervous system (CNS) metastases. But targeted sequencing usually requires at least 5 ng of cfDNA. Due to the limited amount of cerebrospinal fluid (CSF) that can be collected there are not many samples that can meet the requirements of targeted sequencing. Methods: This study assessed the use of shallow whole-genomic sequencing (sWGS) of blood and CSF samples obtained from 35 patients with lung cancer to identify tumor-derived cfDNA. Among them, 6 cases had no intracranial metastasis, 22 had only PMs, and 7 had LMs. Some of these cases underwent irregular follow-up. For blood samples, 5 ng cfDNA was used for library preparation. For CSF samples, try to use trace DNA to prepare libraries, regardless of whether the Qubit assays can quantify the concentration. Cytologic analysis was also performed on CSF samples from the LM cases. A total of 35 peripheral blood samples and 31 cerebrospinal fluid samples were subjected to sWGS tests, and the arm-level CNV and tumor proportion were analyzed.Cytologic analysis was also performed on CSF samples from the LMs. Results: The lowest concentration of cfDNA in 35 plasma samples was 2.20 ng/mL. But when the cfDNA was extracted from the CSF, 50% (6/12) of the LM samples and 70.59% (12/17) of the samples with only PMs could not be quantified by Qubit assays. All libraries were all successfully prepared from the samples that could not quantify cfDNA. For CSF samples from LM cases, the sensitivity of detecting tumor signals by the sWGS test was 90.9% (10/11), higher than 81.8% (9/11) by CSF cytologic analysis. For samples from PM cases, the sensitivity of detecting tumor signals by the sWGS test was 75% (21/28); among them, the detection sensitivity of samples with a total amount of cfDNA not less than 5 ng was 90% (9/10), while the detection sensitivity of samples with the total amount of cfDNA less than 5 ng was 66.67% (12/18). Three patients underwent multiple CSF cfDNA tests, of which one case with RANO evaluation as PR had a decrease in the tumor fraction in CSF cfDNA, while only one of the two cases with RANO SD evaluation had stable tumor fraction in CSF cfDNA. Conclusions: We established a method for detecting CNVs by sWGS using trace amounts of cfDNA. Using the sWGS test improves the sensitivity of the detection of LMs. Compared with targeted capture sequencing, our method reduces the requirement for the amount of cfDNA, which can be more widely used in the detection of CNS metastases, especially in PM-only patients with extremely low CSF cfDNA concentrations.
The impact of the COVID-19 pandemic on the diagnosis and treatment of breast cancer at a community hospital.
Authors: Matthew McGee, Barbara Bennie, Alec Fitzsimmons, Andrea Arenz, Leah L. Dietrich
Journal: Journal of Clinical Oncology (2023)

e18718 Background: COVID-19-related physical distancing restrictions impacted the delivery of close-contact healthcare care in the initial months of the pandemic. To ascertain the effect of these changes on breast cancer (BC) care at Gundersen Health System (GHS), we compared stage at diagnosis (dx), interval between dx and initiation of treatment (tx), and modality of first tx offered to pts (pts) diagnosed with BC before, during, and after pandemic-related restrictions. Methods: We performed a retrospective review of the electronic health records of approximately 904 pts with a new BC dx at GHS. Based on the timing of COVID-19-related restrictions at GHS, we designated any date from January 1, 2019 - March 31, 2020 as “Pre-COVID”, April 1, 2020 - December 31, 2020 as “COVID”, and January 1, 2021 - March 31, 2022 as “Post-COVID”. The median time to first tx for each modality of tx was compared using Kruskal-Wallis tests. Cox proportional hazard models were used to investigate patterns in the time to tx for various tx modalities in the three time periods of interest while accounting for clinical stage at dx. Changes in the distribution of modality of first tx, cancer stage at dx, type of surgery, and mode of disease detection across the three time periods of interest were assessed using Chi-square tests of association. Results: The median time to surgery for pts with surgery as first tx modality was significantly different between time periods (p &lt; 0.001) with time to surgery shortest pre-COVID and longest post-COVID. Significant differences in time to first chemotherapy tx were noted for clinical stage 2 pts (p = 0.002), but not for pts diagnosed at other stages. No differences were noted in times to first hormone therapy tx (p = 0.28). There were significant differences in the distribution of modality of first tx (p &lt; 0.001), the clinical stage at dx (p = 0.01), and the mode of detection (p = 0.04) across the three time periods. These differences reveal a shift in the typical paradigm of BC care due to the pandemic; with a delay in detection and tx, change in clinical stage at dx, and a change in the modality of the first tx. Conclusions: Our data illustrate the effect the pandemic had on routine BC care during and after the pandemic-related restrictions regarding time to first tx, clinical stage at the time of dx, and initial tx modality. Furthermore, these pandemic changes are ongoing with the time to first tx longer in the post-pandemic period as compared to pre-pandemic period. This delay in return to pre-pandemic standards may be due to continued issues with supply chain and staffing shortages. Identifying differences attributable to the pandemic will help guide future decisions regarding BC care should conditions necessitate the reimplementation of strict infection-prevention measures. Identifying issues that continue post-COVID will help determine strategies to close those care gaps.
Efficacy and safety of pembrolizumab plus chemotherapy and sequential surgical resection in initial unresectable stage IIIB NSCLC.
Authors: Jianya Zhou, Yuekang Li, Jing Zheng, Kexin Ruan, Jianying Zhou
Journal: Journal of Clinical Oncology (2023)

e20595 Background: Neoadjuvant immunochemotherapy has been proved effective in resectable NSCLC, while its role in unresectable stage IIIB NSCLC remains controversial. This study aims to demonstrate the efficacy and safety of neoadjuvant immunochemotherapy sequential surgical resection in initial unresectable stage IIIB NSCLC patients. Methods: This multicenter study retrospectively analyzed 59 patients with initial unresectable stage IIIB NSCLC who received induction pembrolizumab combined with chemotherapy between June 2019 and April 2022. The clinical characteristics, radiological and pathological response and survival outcomes were collected and evaluated. Results: A total of 59 initial unresectable stage IIIB NSCLC patients were identified and divided into the surgery group (n = 23) and non-surgery group (n = 36) with a median follow-up time of 15.0 months. The median PFS/DFS of surgery group was significantly longer than that of non-surgery group (not reached versus 15.5 months, p = 0.0031). The median OS was not reached in both groups, overall survival rate was 100% (23/23) in surgery group and 83.3% (30/36) in non-surgery group. Pathological analysis suggested that 13 of 23 patients (56.5%) achieved major pathological response (MPR) or pathological complete response (pCR), and more squamous cell carcinoma cases were observed in MPR group compared to non-MPR group ( p = 0.034). Of 23 patients in surgery group, all patients had a R0 resection, no surgical-related mortality was recorded, only 3 patients (13.0%) experienced any postoperative complications. Conclusions: Surgical resection after neoadjuvant immunochemotherapy is beneficial in the survival outcome of initial unresectable stage IIIB NSCLC patients, with a high MPR rate and good surgical safety.
Racial disparities in aging-related comorbidity among breast cancer survivors.
Authors: Kirsten Nguyen, Cong Wang, Jill De Vis, Mason Alford, Marjan Rafat, Anuradha Bapsi Chakravarthy, Xiao-Ou Shu
Journal: Journal of Clinical Oncology (2023)

10555 Background: Black breast cancer (BC) patients have a higher mortality rate than their white counterparts, potentially due to age acceleration caused by cancer and its treatments. However, epidemiological evidence is limited. Methods: Our study includes 1885 BC patients and 1224 cancer free women (controls) recruited at Vanderbilt University Medical Center from 2004 to 2021. Patient demographics and aging-related outcomes were extracted from the tumor registry or electronic health records. Aging-related outcomes included 28 comorbidities and the Charlson Comorbidity Index (CCI) at baseline (biopsy) and follow-up (latest clinical visit). The associations of BC status with CCI and specific comorbidities were evaluated by linear and logistic regression models, respectively. The associations of race with aging-related outcomes were evaluated among cases. All analyses were adjusted for age, and follow-up outcomes were adjusted for baseline information. Results: The median follow-up time is 10 years. BC patients had a higher mean CCI at baseline (1.32 vs 0.59, p&lt;0.01) and follow-up (beta=1.04, 95% CI=0.94-1.14) than controls. Results from individual comorbidities showed that BC survivors had a higher risk of developing cardiovascular disease, liver disease, hypertension, hyperlipidemia, gastroesophageal reflux disease (GERD), and depression. Among BC patients, Black women were diagnosed at a younger age (52.0 vs 55.8, p&lt;0.01), but had a higher baseline and follow-up CCI than Whites. Black BC survivors were more likely to develop peptic ulcer disease, diabetes, second malignancy, hypertension, and GERD than White BC survivors, even after adjustment for baseline comorbidities. [Table: see text]
Docetaxel as a subsequent line after progression to platinum-based chemotherapy and immunotherapy.
Authors: Yago Garitaonaindia, Virginia Calvo, Isabel Redondo, Maria Uribarren, Aylen Vanessa Ospina Serrano, Ana Collazo, Mariola Blanco, Carla Lozano, Marta Martinez Cutillas, Marta Manso, CRISTINA TRASEIRA, Ramon Aguado, Maria Matilde Sanchez del Corral, Mariano Provencio
Journal: Journal of Clinical Oncology (2023)

e21197 Background: Docetaxel was the standard of care for patients with non-small cell lung cancer (NSCLC) after platinum-based chemotherapy failure. The introduction of immune checkpoint inhibitors (ICIs) has radically altered the first-line treatment for advanced/metastatic NSCLC without driver mutations. However, limited clinical data are known after failure of chemotherapy and immunotherapy. Efficacy of docetaxel after progressing to platinum-based chemotherapy and checkpoint inhibitors are scarce. The aim of this study is to evaluate docetaxel in patients with advanced NSCLC after chemotherapy and ICIs failure in a real-world scenario. Methods: Retrospective, single centre study, including patients treated with docetaxel after progression to platinum-based chemotherapy and immunotherapy. We analysed demographic characteristics, treatments received and survival. Long survivors to Docetaxel were defined as those who lived more than 12 months after initiating Docetaxel. Results: 65 patients were included in this study. Median age was 67.0 years and 67.7% were male. 63.1% were adenocarcinoma, 24.6% squamous-cell carcinoma and 12.3% other histologies. Objective response rate (ORR) for docetaxel was 21.0%, with a control disease rate of 42.1%. 55.7% experienced toxicity from the treatment. Median progression-free survival (PFS) and overall survival (OS) were respectively 2.0 months (1.3-2.7, IQ 95%) and 6.0 months (4.6-7.4, IQ 95%). 16 patients (24.6%) were long survivors. Differential characteristics of long survivors are shown in Table. Conclusions: Docetaxel displayed poor survival results in our study after progression to platinum-based chemotherapy and ICIs, arising the necessity of developing new therapies for this scenario. Despite these results, almost 25% of the patients lived more than one year. Objective response to docetaxel was significantly associated with surviving more than one year, and better ECOG and lacking hepatic metastases showed a non-significant trend. Clinical biomarkers predicting benefit of Docetaxel in this scenario are lacking. [Table: see text]